Innovative research has begun to elucidate the role of individual fatty acids (FA) in human health. Historically, FA research has focused on broad categories of dietary fats, e.g. saturated, polyunsaturated, or monounsaturated fats, and relied on self-reported estimates from diet questionnaires. It is increasingly clear that such broad categorizations are estimated with error and, perhaps more importantly, obscure major differences in health effects of individual FA within these categories. Also, dietary estimates of fat intake provide little information on many other individual FA that in the human body are largely derived from endogenous metabolic processes rather than from direct dietary intake. Consequently, our prior work (R01- HL085710) has focused on circulating FA biomarkers that provide objective measures of exposure to both dietary and metabolic FA. We have found several key individual FA to be significantly associated with major cardiovascular disease (CVD) outcomes, including congestive heart failure (CHF), atrial fibrillation (AF), coronary heart disease (CHD), and stroke. Notably, we identified relations for FA that are largely derived from diet and FA largely derived from metabolic processes. Experimental studies support these findings, with effects of these and other individual FA on a variety of cellular functions and metabolic pathways. Together these results support key potential roles of individual FA in human health. Several fundamental questions remain. To date, all studies of FA biomarkers and CVD risk have utilized only a single baseline measure of exposure, typically among participants in middle-age. Because risk of CVD accelerates dramatically with age, these prior investigations of FA biomarkers in middle-age preclude strong inference on potential effects later in life. Our prior work in the Cardiovascular Health Study (CHS) thus focused on older men and women age 65 at baseline. Whereas this work produced several novel findings, the potential influence of FA on health much later in life, e.g., in the oldest of the old, average age 80- 85 and beyond, is not established. This represents a sizeable and rapidly growing segment of the US, in whom knowing how to prevent CVD and increase healthy aging is critical. Aging is marked by changes in diet, lifestyle, and metabolism, each of which influences circulating FA. Also, as with other risk factors, health effects of FA may vary with aging. Our prior work has confirmed that, for many individual FA, circulating levels change considerably over time. Thus, assessment of FA late in life is crucial to elucidate their potential influence on health in this population. This proposal will build upon and extend our prior work by assessing objective FA biomarkers in CHS at 6 years and 13 years after our initial measures to provide crucial insights into how specific individual dietary and endogenous FA relate to CVD and healthy aging later in life. This work will advance scientific understanding of how FA influence CVD, mortality, and healthy aging and inform innovative targets and interventions for lifestyle, policy, and drug treatment efforts later in life.